How should kidney function be monitored during Lenalidomide therapy?

Serum creatinine/CrCl at baseline and before dose escalation; CBC (cytopenias track exposure) at least monthly; Electrolytes including phosphate if tubular dysfunction suspected; Tumor-lysis labs early in high-burden disease.

How can kidney injury from Lenalidomide be prevented?

Adjust starting dose to creatinine clearance (see dosing) Maintain hydration; tumor-lysis precautions in high-burden disease

Who is at higher risk of kidney injury from Lenalidomide?

Pre-existing renal insufficiency (drives exposure and toxicity); Plasma-cell dyscrasia with nephrotoxic paraproteins; Fixed (non-adjusted) dosing in reduced renal function; High tumor burden (tumor flare/lysis).

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Printable monograph

Immunomodulatory drug (IMiD)

Lenalidomide

Revlimid · LEN

Immunomodulatory drug (IMiD) · approved 2005 · 9 citations

Up to date· through 2025

Deeply sourced7/9 · 6 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 18y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
Not met: Real-world FAERS signal

Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.

A renally cleared immunomodulatory drug where dose adjustment by CrCl is central and AKI, Fanconi, and tumor flare can complicate kidney care.

ModerateImmunomodulatory drug (IMiD)

Multiple myelomaMyelodysplastic syndrome with del(5q)Mantle cell lymphomaFollicular and marginal zone lymphoma

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

AKI/azotemia is uncommon but recognized, described mainly in case series of plasma-cell dyscrasias with underlying renal insufficiency; not reliably quantified as an incidence. Rare Fanconi syndrome and TMA are reported. Because ~80% of lenalidomide is renally cleared as unchanged drug, accumulation in renal impairment is the dominant driver of toxicity, including myelosuppression.Source: Batts et al., Leuk Lymphoma 2008; PK Chen et al., J Clin Pharmacol 2007

Onset & rechallenge

Time to injuryVariable / unpredictable

Azotemia reported from weeks to several months after initiation.

Distilled from: “Variable; azotemia reported from weeks to several months after initiation.”

§02

Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Acute Tubular Necrosis#1 · Signatureno population incidence denominator
AKI, including acute tubular necrosis and acute interstitial nephritis, is the predominant lenalidomide renal toxicity PMID 26927826 (opens PubMed in a new tab)
Fanconi SyndromeRarequalitative — no citable incidence
Global failure of proximal tubule reabsorption — glucosuria, phosphaturia and acidosis, classically from ifosfamide.
Thrombotic MicroangiopathyRarequalitative — no citable incidence
Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityModerate

ReversibilityVariable

Evidence9 citations

Nephron map

Glomerulus

Vasculature / Endothelium

Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)

Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water

Interstitium

Acute Tubular Necrosis

Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

§03

Kidney injury

Appears in 1 documented synergy combination

Mechanism of kidney injury

Mechanisms are incompletely defined. Lenalidomide is eliminated predominantly by glomerular filtration and renal tubular secretion as unchanged drug, so reduced clearance in CKD raises systemic exposure (AUC increased ~185-420% across moderate-to-severe impairment) and amplifies toxicity. Proposed renal-specific contributors include proximal tubular injury (occasionally a Fanconi pattern with phosphate and amino-acid wasting), the combined nephrotoxic burden of paraproteins plus an anti-angiogenic agent, and rarely tumor flare/tumor lysis and TMA.

Clinical presentation

Rising creatinine/azotemia, sometimes progressing to dialysis; rare proximal tubular dysfunction (glucosuria with normoglycemia, hypophosphatemia, aminoaciduria) or TMA features (schistocytes, thrombocytopenia). Tumor flare may present with painful lymphadenopathy and rising LDH early in CLL/lymphoma treatment.

Management

Hold or dose-reduce for AKI and treat reversible contributors (volume, paraprotein, nephrotoxins); monitor renal function and electrolytes. Some cases are irreversible and require dialysis, so early recognition and CrCl-based dose adjustment are essential. For TMA, stop the drug and manage supportively.Lesion-level management framework

Risk factors

Pre-existing renal insufficiency (drives exposure and toxicity)
Plasma-cell dyscrasia with nephrotoxic paraproteins
Fixed (non-adjusted) dosing in reduced renal function
High tumor burden (tumor flare/lysis)

Prevention

Adjust starting dose to creatinine clearance (see dosing)
Maintain hydration; tumor-lysis precautions in high-burden disease

Anticancer mechanism· how it treats cancer

Thalidomide analog that binds cereblon to redirect the CRL4 E3 ubiquitin ligase, triggering ubiquitination and proteasomal degradation of the transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos); this produces direct antimyeloma, anti-angiogenic, and T/NK-cell immunostimulatory effects. Used in multiple myeloma, del(5q) MDS, and certain lymphomas.

Note · Renally cleared - dose adjustment by creatinine clearance is central. AKI incidence is not well quantified and is described at the case-series level.

§04

Clinical depth

Renal dose adjustment

Per pharmacokinetic data, adjust the starting dose when CrCl <60 mL/min (myeloma labeling): CrCl 30-60 use ~10 mg daily; CrCl <30 not on dialysis use 15 mg every other day; on dialysis use 5 mg once daily, given after dialysis on dialysis days. Disease-specific labels differ; titrate to tolerance.

Dialyzability & ESKD dosing

Yes, lenalidomide is removed by hemodialysis - a 4-hour session cleared ~31% of body drug content. Administer the daily dose after the dialysis session on dialysis days.

Differential diagnosis

Separate drug accumulation/ATN from myeloma cast nephropathy (look for the paraprotein and free light chains), from prerenal azotemia (volume responsive), and from rare lenalidomide TMA (MAHA triad). A Fanconi pattern (normoglycemic glucosuria, phosphaturia, LMW proteinuria) points to proximal tubular toxicity.

Monitoring

Serum creatinine/CrCl at baseline and before dose escalation
CBC (cytopenias track exposure) at least monthly
Electrolytes including phosphate if tubular dysfunction suspected
Tumor-lysis labs early in high-burden disease

Key trials & series

Chen et al. renal-impairment pharmacokinetic/hemodialysis study (J Clin Pharmacol 2007)
Batts et al. azotemia case series (Leuk Lymphoma 2008)

Clinical pearls

Lenalidomide is renally cleared - always dose by CrCl and give after dialysis; failing to adjust causes both cytopenias and worsening renal function.
Unlike pomalidomide, lenalidomide exposure rises sharply in CKD, so the two IMiDs are not interchangeable in renal impairment.
New thrombocytopenia plus AKI on lenalidomide should prompt a smear to exclude TMA.

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the Immunomodulatory drug (IMiD) class.

Vascular

Hypertension, VTE/ATE, bleeding, aneurysm

Venous thromboembolism

Hematologic

Cytopenias, thrombosis, TMA

Myelosuppression

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

Neuropathy (thalidomide)

§05

References

6 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

6 references · 2007–2025 · 1 since 2023

Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.

Case reports — ranked by strength· 3

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseB · ModerateLenalidomide-induced acute interstitial nephritis.Lipson EJ et al. · Oncologist 2010 · PMID 20709889First biopsy-proven case of lenalidomide-induced acute interstitial nephritis in a multiple myeloma patient.CaseB · ModerateLenalidomide-induced tubulointerstitial nephritis in Hodgkin lymphoma.Dinh A et al. · Leuk Lymphoma 2019 · PMID 31125280Biopsy-confirmed lenalidomide-induced tubulointerstitial nephritis in a young adult treated for Hodgkin lymphoma.CaseC · LimitedRecurrent Fanconi Syndrome Induced by Lenalidomide: A Case Report.Sharra I et al. · Cureus 2024 · PMID 39108773Lenalidomide-induced recurrent Fanconi syndrome with proximal renal tubular reabsorption defect (glycosuria, phosphaturia, low-molecular-weight proteinuria) in IgG kappa multiple myeloma.

FDA label — boxed warning & renal dosing· boxed warning · renal impairment

Quoted verbatim from this agent's current FDA label (May 2026) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM Embryo-Fetal Toxicity Do not use lenalidomide capsules during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting lenalidomide treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after lenalidomide capsules treatment [see Warnings and Precautions ( 5.1 ), and Medication Guide ( 17 )] . To avoid embryo-fetal exposure to lenalidomide, lenalidomide capsules are only available through a restricted distribution program, the Lenalidomide REMS program ( 5.2 ). Information about the Lenalidomide REMS program is available at www.lenalidomiderems.com or by calling the REMS Call Center at 1-888-423-5436. Hematologic Toxicity (Neutropenia and Thrombocytopenia) Lenalidomide capsules can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q myelodysplastic syndromes had to have a dose delay/reduction during the major study. Thirty-four…

Renal impairment — from the label

Adjust the starting dose of lenalidomide capsules based on the creatinine clearance value and for patients on dialysis [see Dosage and Administration ( 2.6 )] .

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 420,081 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS reported renal phenotypes· 1 signal

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Thrombotic Microangiopathycorroborated · ROR 1.13
Acute Tubular NecrosisNot measurable in reporting — Reporters cannot reliably name this lesion, so its absence from FAERS is expected and is not evidence against the documented injury.
Fanconi SyndromeNo disproportionate reporting — This phenotype IS reportable and this agent has enough reports, yet the reporting is not disproportionate — the one genuinely informative negative of the four.

Thrombotic Microangiopathy

ROR 1.1395% CI 1.01–1.25· 349 reports

FAERS outcomes & reporting trend· 12.8% of reports w/ death · 26% w/ hospitalization

12.8%

Reported with a death outcome

53,762 of 420,081 reports

26%

Reported with hospitalization

109,167 of 420,081 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 9 systems · 420,081 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 0.7795% CI 0.74–0.80· 2,362 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

General / constitutional

Fatigue26,785Asthenia10,124Fall7,514Pyrexia7,262Peripheral Swelling6,764

Gastrointestinal

Diarrhoea31,469Constipation11,085Nausea10,891

Blood & lymphatic

White Blood Cell Count Decreased11,893Platelet Count Decreased9,592Neutropenia9,298Anaemia7,495Thrombocytopenia6,628

Skin

Rash18,227Pruritus7,423

Immune / infection

Pneumonia18,842Covid-196,576

Nervous system

Neuropathy Peripheral12,164Dizziness7,284

Musculoskeletal

Muscle Spasms7,761

Respiratory

Dyspnoea7,675

Vascular

Thrombosis7,546

Guidelines & consensus· 13

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

General onco-nephrology references

ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.SIRMSIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Radiol Med 2022 · PMID 35303246Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.

Where Lenalidomide sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Zoledronic acid

Zometa · Bisphosphonate

Profile

Toxic ATN, infusion-rate dependent.

ATNFANC

Moderate#1 · 62% phenotype match

Vemurafenib

Zelboraf · BRAF inhibitor

Profile

Strongest renal offender of the BRAF/MEK class: proximal tubular injury/Fanconi and early AKI.

ATNFANCLYTE

Moderate#2 · 58% phenotype match

Trastuzumab deruxtecan

Enhertu · Antibody-drug conjugate (HER2/DXd)

Profile

Emerging AKI/proteinuria reports — under-published.

ATNFANCLYTE

Moderate#3 · 54% phenotype match

Oxaliplatin

Eloxatin · Platinum agent

Profile

Least nephrotoxic platinum; rare immune hemolysis.

TMAATN

Mild#4 · 52% phenotype match

BRAF / MEK inhibitors (vemurafenib · dabrafenib · trametinib)

BRAF/MEK inhibitor

Profile

Tubulointerstitial AKI; vemurafenib strongest.

ATNAINLYTE

Mild#5 · 52% phenotype match

Procarbazine

Matulane · Hydrazine alkylating agent

Profile

Classic cytotoxic with recognized renal/urological complications; AKI usually multifactorial; hypersensitivity AIN possible.

ATNAIN

Moderate#6 · 51% phenotype match

Compare Lenalidomide with its nearest agents

Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.

Kidney risk across Other targeted agents

Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.

A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.

Who studies this

The leading contributors to Lenalidomide’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Lenalidomide; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 144 clinical records among all 177 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.